This invention relates to thiophene derivatives, pharmaceutical compositions containing them and methods of using them to treat inflammation and/or pain in mammals. More particularly, this invention relates to antiinflammatory and/or analgesic 2,3-diaryl-5-halo thiophenes.
Compounds of this general type are known in the art, but not as analgesic or antiinflammatory agents. A number of references including J. L. Melles and H. J. Backer, Rec. trav. chim., 72, 314 (1953) and S. Hauptmann and E.-M. Werner, J. prakt. Chem., 314, 499 (1972) disclose the preparation of 2,3-diphenylthiophene.
Melles and Backer, op. cit., describe the preparation of 2-bromo-3,4-diphenylthiophene; 4,5-dibromo-2,3-diphenylthiophene; 3,5-dibromo-2,4-diphenylthiophene and 3,4-dibromo-2,5-diphenylthiophene. U.S. Pat. No. 4,302,461 describes the use of 5-bromo-2,3-diarylthiophenes as intermediates. No biological activity is reported for any of these compounds. U.S. Pat. No. 4,174,405 describes 2-halo-3,5-diarylthiophenes and their use as acaricides.
There is a continuing need for safe and effective antiinflammatory agents. Inflammation is a disease process characterized by redness, fever, swelling, and pain. Arthritis, in its various forms, is the most prevalent, chronic, and severe of the inflammatory diseases. Traumatic injury and infection also involve inflammation, and antiinflammatory drugs are often used in their treatment. The usefulness of most commercial antiinflammatories is limited because of toxicity and adverse side-effects. Many produce gastric irritation and other effects, such as changes in blood cells and central nervous system. Adrenocortical steroids produce gastric irritation and suppression of normal adrenal function.
The present invention results from efforts to develop new antiarthritic compounds with good antiinflammatory activity and minimal side effects that could be more effective in treating arthritis than presently available drugs.
In addition to antiinflammatory properties, some compounds of this invention have demonstrated analgesic activity in a test procedure. This additional property is desirable in treatment of arthritis or related diseases; however, such compounds can be employed solely to alleviate pain.